1. Field of the Invention
The present invention relates generally to the preparation and use of novel enhanced biological tissue adhesives which rely on combining fibrinogen and thrombin. More particularly, the present invention relates to a method of preparing a fibrin sealant whereby said sealant is formed by reconstituting the fibrinogen component in the presence of various critical biological and non-biological agents. The invention further relates to a novel method of using said enhanced fibrin sealant whereby the sealant and accompanying agent are delivered directly to a critical site within the body and sealed in place due to the bio-static quality of the novel sealant resulting in enhanced therapeutic value derived, for example, by the prolonged presence of said accompanying agent at the critical site. The bio-static quality of the novel composition makes it possible to deliver a particular therapeutic agent to a specific critical site within the body and provide for a sustained, time-released delivery of said agent at said critical site.
2. Related Art
Fibrin sealants are well known and used extensively in various clinical settings. Said sealants are indicated as adjuncts to hemostasis in surgeries when control of bleeding by conventional surgical techniques, including suture, ligature, and cautery is ineffective or impractical. For instance, fibrin sealants have been shown to be effective in patients undergoing reoperative cardiac surgery (J. Rousou, et al., Journal of Thoracic and Cardiovascular Surgery, vol.97, no.2, pp 194-203, February 1989), spinal neurosurgery (P. Knoringer, Fibrin Sealing in Spinal Neurosurgery, 1986), general cardiac surgery (P. M. McCarthy, et al., Fibrin Sealant: The Cleveland Clinic Experience, 1991), pulmonary surgery, (M. Dahan et al., The Importance of Biological Glue for the Prevention of Air Leakage in Pulmonary Surgery, Materials and Methods, pp 113-116, 1991), liver and spleen surgery (H.W. Waclawiczek, Fibrin Sealing in Liver and Spleen Surgery, 1994), and neurosurgical procedures (C. Shaffrey, et al., Neurosurgery, vol.26, No.2, pp 207-210, 1990).
Use of fibrin glue and methods for its preparation and use are described by Hirsh et al. U.S. Pat. No. 5,643,192. Hirsh, however, does not envision the reconstitution of the fibrinogen component in the presence of various critical biological and non-biological agents as envisioned by the instant invention. Marx U.S. Pat. No. 5,651,982 describes the preparation and use of fibrin glue and liposomes wherein said liposomes contain various biological agents. Marx, however, describes only topical application of said sealant. Marx does not envision the novel delivery method of the instant invention which delivers critical agents to discrete sites within the body.
It is an object of the present invention to provide an improved fibrin sealant which incorporates various critical biological and non-biological agents into the novel sealant. It is a further object of the present invention to present a novel method of reconstituting fibrin sealant in the presence of said agents to provide a sealant with enhanced therapeutic value. It is a further object of the present invention to provide a method of delivering said enhanced sealant to a discrete site within the body in a manner which takes advantage of the bio-static qualities of fibrin sealant to provide superior therapeutic value to the patient by delivering, sealing and holding said agent at critical sites within the body. Optionally, said agent is then slowly released or absorbed at said specific site providing maximum therapeutic value.